An evaluation of some of the mechanisms underlying the physiological regulation of the fibrinolytic enzyme system will be undertaken. The proposed research will focus on two regulatory aspects: 1) those human plasma inhibitory factors which tend to buffer the active enzyme plasmin; and 2) those elements involved with the production and maintenance of circulating levels of zymogen, plasminogen. Using highly purified human enzyme and inhibitor preparations, a systematic and comparative study will be made of the kinetics of plasmin inhibition by each of the plasma protease inhibitors. The methods involved will focus primarily on enzymatic assays and gel electrophoresis. In addition, the relative contributions that each of the inhibitors makes to the total antiplasmin inhibitory capacity of plasma will be determined using a whole plasma system and radiolabelled proteins. The interaction of these inhibitors with the activation of plasminogen to plasmin will also be studied.